17 October 2016

outline

  • definitions: virulence and all that
  • transmission modes
  • tradeoff theory
  • beyond the tradeoff theory

definitions and context

definitions of virulence

  • something bad about an infectious disease (media/general public)
  • infectivity (plant/molecular biology)
  • decrease in host fitness (evolutionary biology)
  • rate of disease-induced mortality (link host, parasite fitness)

other properties

  • host castration
    (host fitness \(\searrow\) without death)
  • parasite clearance by host (immunity)
    (parasite fitness \(\searrow\))
  • case mortality
    (probability of host death)
  • immunopathology
    (host and parasite fitness \(\searrow\)?)

Q: which of these represent virulence?

other aspects of host-parasite interaction

  • virulence depends on both host and parasite

  • exploitation (parasite)
  • pathogenesis (parasite)
  • resistance (host)

  • tolerance (host)

classical theory and its problems

classical theory

Parasites evolve lower virulence over time for the good of the species; don't want to hurt host

Given enough time a state of peaceful coexistence usually becomes established between any host and parasite … throughout nature, infection without disease is the rule rather than the exception (Dubos, 1980)

For nature, survival of the species is all that counts (Macfarlane Burnet & White, 1972)

evolution …

  • variation in parasite fitness (between-host replication rate)
  • relationship between parasite traits and fitness
  • heritability of parasite traits

classical theory: evidence? examples?

  • syphilis (Knell, 2004)

  • virgin-soil epidemics

  • what other factors might explain virulence of new outbreaks?

  • counterexamples: malaria, tuberculosis …

Wikipedia

problems with classical theory

  • group selection
  • effect of cheaters: why not drive the host population to extinction?


George Williams

tradeoff theory

tradeoff theory

  • intermediate virulence evolves due to host-level selection
  • tradeoff between transmission rate (infections/host/time) and virulence (mortality/time)
  • \(R_0\) (total transmission per generation) maximized at intermediate virulence

modes of transmission

Modes of transmission may drive parasite evolution

  • environmental (e.g. water)
  • vector-borne
  • needle-borne
  • direct transmission
  • vertical transmission
  • necrotransmission (e.g. anthrax)

what's your prediction about nosocomial (hospital-borne) transmission?

source

myxomatosis

  • Viral disease; mild in Brazilian rabbits (Sylvilagus brasiliensis); virulent in European rabbits (Oryctolagus cuniculus)
  • Vector-borne (by mosquitos and fleas)
  • Introduced (several times) in Australia to control introduced rabbits, finally spread 1950-1951.

Wikipedia, Richard Harvey

myxomatosis (cont.)

  • Case mortality originally >99%, rabbit pops initially \(\searrow\) 90%
  • CM initially dropped to 90%, then further
  • Resistance: CM of grade III strain drops from 90% to about 50% as populations experience more epizootics.
  • At the same time mean virus grade drops from I to III, then rebounds

myxomatosis virulence over time
(Fenner et al., 1956)

evidence for tradeoff theory:

  • Higher grades (higher case mortality) also have faster mortality (<13 days to >50 day survival as CM goes from >99% to <50%).
  • Skin virus titer is also higher (and increases faster with time) for higher grades.
  • Mosquito infection probability is proportional to skin titer

Bottom line: myxomavirus probably still reduces populations somewhat, but the Australians are looking for other biocontrol solutions (calicivirus).

tradeoff theory

Maximizing \(R_0\):

beyond the tradeoff theory
(Ebert & Bull, 2003)

  • within-host competition will generally increase virulence
    (when is this likely to happen?)
  • coincidental virulence: spillover epidemics
  • short-sighted evolution: e.g. meningitis (Levin & Bull, 1994)
  • spatial structure/limited dispersal (Boots & Mealor, 2007)
  • the devil is often in the details

testing theories

  • real-world experiments are hard! (ethics, logistics, time …)
  • laboratory evolution (Berngruber et al., 2013)
  • build models

HIV virulence evolution

HIV within-host 'life history'

evolution of HIV virulence
(Shirreff et al., 2011)

HIV virulence: model sensitivity

References

Berngruber, T. W., Froissart, R., Choisy, M., & Gandon, S. (2013). Evolution of virulence in emerging epidemics. PLoS Pathog, 9(3), e1003209. http://doi.org/10.1371/journal.ppat.1003209

Boots, M., & Mealor, M. (2007). Local interactions select for lower pathogen infectivity. Science, 315(5816), 1284–1286.

Dubos, R. J. (1980). Man Adapting. Yale University Press.

Ebert, D., & Bull, J. J. (2003). Challenging the trade-off model for the evolution of virulence: Is virulence management feasible? Trends Microbiol, 11(1), 15–20.

Fenner, F., Day, M. F., & Woodroofe, G. M. (1956). Epidemiological consequences of the mechanical transmission of myxomatosis by mosquitoes. J Hyg (London), 54(2), 284–302.

Knell, R. J. (2004). Syphilis in Renaissance Europe: Rapid evolution of an introduced sexually transmitted disease? Proc R Soc London B, 271, S174–S176.

Levin, B. R., & Bull, J. J. (1994). Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol, 2, 76–81.

Macfarlane Burnet, F., & White, D. O. (1972). Natural History of Infectious Disease. CUP Archive.

Shirreff, G., Pellis, L., Laeyendecker, O., & Fraser, C. (2011). Transmission selects for HIV-1 strains of intermediate virulence: A modelling approach. PLoS Computational Biology, 7(10), e1002185. http://doi.org/10.1371/journal.pcbi.1002185